Introduction

Uses for Vedolizumab

Ulcerative Colitis

Used to induce and maintain clinical response and clinical remission, improve endoscopic appearance of mucosa, and achieve corticosteroid-free remission in adults with moderately to severely active ulcerative colitis who have had an inadequate response to, have lost response to, or were intolerant to a tumor necrosis factor (TNF) blocking agent or immunosuppressive agent (e.g., azathioprine, mercaptopurine), or who have had an inadequate response to, were intolerant to, or have demonstrated dependence on corticosteroids.1256

Crohn's Disease

Used to achieve clinical response, clinical remission, and corticosteroid-free remission in adults with moderately to severely active Crohn's disease who have had an inadequate response to, have lost response to, or were intolerant to a TNF blocking agent or immunosuppressive agent (e.g., azathioprine, mercaptopurine, methotrexate), or who had an inadequate response to, were intolerant to, or have demonstrated dependence on corticosteroids.11214

General

Aminosalicylates, corticosteroids, and immunosuppressive agents (azathioprine, mercaptopurine) could be continued in clinical studies in patients with ulcerative colitis.16

Aminosalicylates, corticosteroids, antibiotics, and immunosuppressive agents (azathioprine, mercaptopurine, or methotrexate) could be continued in clinical studies in patients with Crohn’s disease.112

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 Do not administer by rapid IV injection (IV push or bolus).1

Do not mix with or administer through the same administration set with other drugs.1

Flush IV line with 30 mL of 0.9% sodium chloride injection after the infusion is complete.1

Lyophilized powder must be reconstituted at room temperature and diluted prior to administration.1

Reconstitution

Reconstitute vedolizumab lyophilized powder by adding 4.8 mL of sterile water for injection (using a syringe with a 21- to 25-gauge needle) to a 300-mg vial to provide a solution containing 60 mg/mL.1 Direct diluent toward wall of vial to avoid excessive foaming.1

Gently swirl vial for at least 15 seconds to dissolve powder.1 Do not shake vigorously or invert.1 Allow solution to stand for up to 20 minutes at room temperature to allow for reconstitution and for any foam to settle.1 Vial can be swirled and inspected for dissolution during this time.1 If not fully dissolved within 20 minutes, allow an additional 10 minutes.1 Do not use vial if drug is not dissolved within 30 minutes.1

Hypersensitivity reactions may include dyspnea, bronchospasm, urticaria, flushing, rash, and increased BP and heart rate; anaphylaxis also reported.1 Experience with other biologic agents suggests that time of onset may be variable (during, immediately after, or several hours after an infusion).1

Clinicians should be prepared to treat hypersensitivity and infusion-related reactions.1 Ensure appropriate equipment and agents for treating such reactions are available for immediate use, and monitor patient until infusion is completed.1 If anaphylaxis or other serious allergic reactions occur, immediately discontinue the infusion and initiate appropriate treatment (e.g., epinephrine, antihistamines).1

Infectious Complications

Increased risk of infections.1 Most common infections are nasopharyngeal and upper respiratory tract infections.1561214 However, serious infections (e.g., anal abscess, sepsis [sometimes fatal], tuberculosis, Salmonella sepsis, Listeria meningitis, giardiasis, cytomegaloviral colitis) also reported, more commonly in patients with Crohn's disease than in those with ulcerative colitis.114

In clinical trials in ulcerative colitis and Crohn's disease, rate of infection was 0.85 or 0.7 per patient-year in patients receiving vedolizumab or placebo, respectively; rate of serious infection was 0.07 or 0.06 per patient-year, respectively.1 Rate of serious infection did not increase over 48 months.1

Delay initiation of vedolizumab until any active severe infection has been controlled.1 If severe infection develops during therapy, consider interrupting vedolizumab therapy.1

Exercise caution when considering use in patients with a history of recurring severe infections.1

Consider screening for active or latent tuberculosis infection.1

Progressive Multifocal Leukoencephalopathy (PML)

PML, an opportunistic infection of the brain caused by the JC virus, reported in patients receiving natalizumab, an anti-α4-integrin monoclonal antibody.120 PML generally occurs only in immunocompromised patients and usually progresses to death or severe disability.1 Patients in vedolizumab clinical trials were actively monitored for PML; although no cases reported among patients exposed to the drug for ≥24 months, risk of PML cannot be ruled out and safety of vedolizumab relative to other integrin receptor antagonists not fully established.1

Monitor for any new or worsening neurologic manifestations (see Advice to Patients).1 If PML is suspected, withhold drug and refer patient to a neurologist.1 Permanently discontinue if PML is confirmed.1

Hepatic Effects

Increases in serum ALT and AST concentrations and/or bilirubin concentrations, including several cases of hepatitis, reported following 2–5 doses of the drug; unclear whether reactions were drug induced or autoimmune.1 All patients recovered following drug discontinuance, although some patients also required corticosteroid treatment.1

Discontinue vedolizumab in patients with jaundice or other evidence of clinically important hepatic injury.1

Immunization

Administer all appropriate vaccines as recommended by current immunization guidelines prior to initiation of vedolizumab.1

Malignancies

Malignancies (excluding dysplasia and basal cell carcinoma) reported in 0.4 or 0.3% of patients receiving vedolizumab or placebo, respectively, during clinical trials in ulcerative colitis or Crohn's disease.1 Malignancies also reported during extension phases of the trials; however, data regarding effects of long-term exposure to the drug are limited.1

Immunogenicity

Formation of antibodies, including neutralizing antibodies, to vedolizumab reported.1 Presence of persistently positive anti-vedolizumab antibodies associated with undetectable or negligible serum concentrations of the drug and failure to achieve clinical remission.1

Specific Populations

Pregnancy

Category B.1 Any adverse effect on pregnancy outcomes likely would be greater during second and third trimesters, since monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses.1

Pregnancy registry at 877-825-3327.1

Lactation

Distributed into milk in monkeys; not known whether distributed into human milk.1 Use with caution.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; however, no overall differences in efficacy and safety observed.1

Interactions for Vedolizumab

Vaccines

Inactivated vaccines: For IM hepatitis B vaccine and oral inactivated cholera vaccine (not commercially available in US), see Specific Drugs under Interactions. Effect of vedolizumab on immune responses to other oral or intranasal vaccines not known.1 Manufacturer states patients receiving vedolizumab may receive inactivated vaccines.1

Live vaccines: No data on secondary transmission of infection by live vaccines in patients receiving vedolizumab.1 Manufacturer states patients receiving vedolizumab may receive live vaccines if potential benefits justify possible risks.1

Specific Drugs

Drug

Interaction

Comments

Cholera vaccine, oral inactivated

Single vedolizumab dose given 4 days before initiation of immunization series reduced seroconversion rate and titers of antibody to cholera toxin121

May be used concomitantly1

Hepatitis B vaccine

Single vedolizumab dose given 4 days before initiation of IM immunization series did not affect seroconversion rate121

Stability

Storage

Parenteral

Powder for IV Infusion

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility1

Compatible

Sodium chloride 0.9%

Actions

Binds specifically to α4β7 integrin, a protein expressed on the surface of a small subset of memory T-lymphocytes that preferentially migrate into the GI tract.12456789101213141516 Binding of vedolizumab to α4β7 integrin blocks interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed mainly on vascular endothelial cells in the GI tract, and inhibits migration of memory T-lymphocytes across the endothelium into inflamed GI parenchymal tissue.158

Interaction of α4β7 integrin with MAdCAM-1 implicated as an important contributor to the chronic inflammation of ulcerative colitis and Crohn's disease.1

Does not bind to or inhibit the function of α4β1 and αEβ7 integrins; does not antagonize the interaction of α4 integrins with vascular cell adhesion molecule-1 (VCAM-1).1

Appears to exert a more selective effect on the GI tract than does natalizumab, which binds to α4 subunits of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils.781620

Advice to Patients

Importance of immediately reporting symptoms consistent with a hypersensitivity reaction (e.g., rash, pruritus, shortness of breath or difficulty breathing, wheezing, dizziness, flushing, palpitations, swelling of lips, tongue, throat, or face) that occur during or following IV infusion of the drug.1

Potential for PML to occur in patients who receive a different integrin receptor antagonist.1 Importance of immediately informing clinician of any new or worsening neurologic manifestations (e.g., progressive weakness on one side of body or clumsiness of limbs; changes in speech or walking; vision changes; changes in thinking, memory, and orientation leading to confusion and personality changes).1

Importance of reviewing vaccination status with clinician and receiving all age-appropriate vaccines prior to initiation of vedolizumab therapy.1

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., liver disease, tuberculosis or other infection) or any history of recurrent infections.1

Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 (See Pregnancy Under Cautions.)

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.